What is Genomics

Final Draft

What is Genomics?

      Genomics is the study of genomes. A genome is the entire DNA code found in the chromosomal set of an organism.  A comprehensive study of a genome would include three parts: (1) structural genomics, (2) functional genomics, and (3) comparative genomics (Brown, 2006).  This essay presents a short review of the three steps for a complete genome analysis.

The study of a genome begins with an examination of the sequence, or structural analysis.  A structural analysis refers to determining the sequence and location of each genetic element on a given DNA sequence. This is done by molecular and computing techniques including sequencing and assembly respectively.  Today, there are several sequencing techniques used for the study of genomes, but the first technique applied was the Sanger method (Sanger and Coulson, 1975).  Sanger sequencing method is based on a chain termination reaction that involves synthesis of DNA strands complementary to a single- stranded DNA template. The end product of this process is a library of short DNA fragments. To reconstruct the whole genome, these fragments have to be arranged together to form a long continuous sequence, in a process called sequence assembly (Myers et al., 2000).   
The ultimate goal of structural genomics is to identify every gene in the genome assembly.  Sequence inspection can be used to locate genes because they are not random series of nucleotides (structural units of DNA), but can be recognized for their distinctive features.  Since genes code for proteins, these features are well known.  For example, genes always start with a specific sequence, the initiation codon (ATG).  This codon (a three-nucleotide sequence that codes for one amino acid) codes for the amino acid methionine (Met) found at the beginning of each protein (Brown, 2006).
The issue of finding genes is actually more complicated, because they are not continuous, and are often interrupted by the non-coding sequences called introns. Fortunately, these elements can also be identified, because they share common features between genes.  Finally, gene sequences always end with a termination codon (for example: UGA). Termination codon interrupts the process of transcription (copying of DNA into RNA), and thus always ends a gene.  The sequence identified in this manner between initiation and termination codon is called an open reading frame (ORF).  Once all the genes have been located, a complete structural analysis of the genome has been completed.  

As part of a genome study, it is required to narrow down the study and focus in a chromosome and the genes that it contains.  By doing this, it is easier to find the functions of the genes; this part is known as functional genomics.  As the genes regularly have many different functions, this task is often difficult.  
There are several approaches to determine the function of a gene.  For example, a common procedure is gene silencing, a method that uses mutations that change the original function of the gene and observe what happens to the organism (McManus and Sharp, 2002). The result of gene silencing is termination of gene expression which provides insights into the function.  Another way to determine gene function is to study the differences caused by the distinct alleles (an alternate form of a gene) of the same gene.  Usually, there is a common allele, or wild type, encoded by a certain sequence of a gene.  Individuals with genetic mutations in a gene sequence are compared to the wild type to see if they cause changes in function.  In addition, the location of gene expression can also be relevant to the gene function.  By observing where the gene is expressed within the organism, its purpose can be determined.  Usually, this is done either by attaching fluorescent tags to the sequences and tracking them with a microscope (Chalfie et al., 1994), or by identifying the increase in the amounts of the relevant RNA or protein in tissues (VanGuilder et al., 2008).  For example, if the protein that the gene encodes is found in the brain, then its function has to do with the brain activity.  Finally, the data gathered from the approaches described above can be used to study genetic pathways, in other words, tracking interactions between different genes. The goal of functional genomics is to determine gene function, to know how all the genes in an organism work, and to establish all the characteristics it has.

The final approach of the comprehensive genome study is comparative genomics. This area focuses on comparisons of genomes between related species and determines how they differ in structure and function.  This part of genomics is concerned with evolutionary processes, which describe how genomes acquired their structure.  It has been observed that different organisms often carry the same genes known as homologous.  Even distantly related organisms share common genes because of their common ancestry. Genes that are important change slowly because random changes can disturb their function, while genes that are not so critical change faster, and are found to be more different when compared between species (Oleksyk et al., 2010). This is an important point, because comparative analysis of genome sequences can point out the important genes maintained by selection. On the other hand, finding genes that are divergent between species can explain differences between them.  For example, comparisons between the human genome and that of the chimpanzee, shows genes that are involved in developing superior brain structure and allows humans to use speech (Enard et al., 2002; Fisher and Scharff, 2009).  In other words, comparative genomics can give a scientific answer to one of the most important questions: “what makes us human”?

In short, this essay has reviewed the three stages of the study of a genome.  Together they are combined in Genomics, a science that studies genomes, the entire DNA codes found in each of the chromosomes that a given organism carries.  A comprehensive genome study involves all three major parts: structural genomics, functional genomics and comparative genomics.  Structural genomics focuses in sequencing and assembly of the genome for gene location.  Functional genomics is the area that determines that function of the genes.  Finally, comparative genomics focuses on comparing genomes of related species to determine the differences and similarities found between them.

Works Cited

Brown T.A. (2006). Genomes 3. 3rd ed. Garland Science Publishers. Oxford.713p.

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Enard W, Przeworski M, Fisher SE, Lai CS, Wiebe V, Kitano T, Monaco AP, Pääbo S (2002). "Molecular evolution of FOXP2, a gene involved in speech and language". Nature 418 (6900): 869–72.

Fisher SE, Scharff C (2009). "FOXP2 as a molecular window into speech and language". Trends Genet. 25 (4): 166–77

McManus, M.T. & Sharp, P.A. (2002) “Gene silencing in mammals by small interfering RNAs”. Nature reviews. Genetics 3, 737-47

Myers EW, Sutton GG, Delcher AL, et al. (2000). "A whole-genome assembly of Drosophila". Science 287 (5461): 2196–204

Oleksyk TK, Smith MW, O'Brien SJ (2010) “Genome-wide scans for footprints of natural selection”.  Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 365(1537):185-205.

Sanger F, Coulson AR (1975). "A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase". J. Mol. Biol. 94 (3): 4418

VanGuilder H D, Vrana KE, Freeman WM (2008). "Twenty-five years of quantitative PCR for gene expression analysis". Biotechniques 44 (5): 619–626